Polygenic risk scores in atrial fibrillation: Associations and clinical utility in disease prediction

Atrial fibrillation (AF) is a common heart arrhythmia and a major cause of cardioembolic stroke. Therefore, accurate prediction is desirable to allow high-risk individuals to be identified early and their risk lowered before complications arise. Polygenic risk scores (PRSs) have become a popular method of quantifying aggregated genetic risk from common variants, but their clinical value in AF remains uncertain. This literature review summarizes the associations between PRS and AF risk and discusses the evidence for the clinical utility of PRS for AF prediction. Stroke risk in patients with AF is also considered. Despite consistent associations between PRS and AF risk, the performance of PRS as a stand-alone tool for AF prediction was poor. However, addition of PRS to the existing AF prediction models commonly improved the predictive performance above that of the clinical models alone, including in cohorts with comorbid cardiovascular disease. Associations between PRS and cardioembolic stroke risk in patients with AF have also been reported, but improvements in stroke prediction models from PRS have been minimal. PRS are likely to add value to the existing clinical AF prediction models; however, standardization of PRS across studies and populations will likely be required before they can be meaningfully adopted into routine clinical practice.